Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

Background: The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD. Methods: Thirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells). Results: At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal. Conclusions: In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission

Architectural Decision Management for Digital Transformation of Products and Services

The digitization of our society changes the way we live, work, learn, communicate, and collaborate. The Internet of Things, Enterprise Social Networks, Adaptive Case Management, Mobility systems, Analytics for Big Data, and Cloud services environments are emerging to support smart connected products and services and the digital transformation. Biological metaphors of living and adaptable ecosystems provide the logical foundation for self-optimizing and resilient run-time environments for intelligent business services and service-oriented enterprise architectures. Our aim is to support flexibility and agile transformations for both business domains and related information technology. The present research paper investigates mechanisms for decision analytics in the context of multi-perspective explorations of enterprise services and their digital enterprise architectures by extending original architecture reference models with state of art elements for agile architectural engineering for the digitization and collaborative architectural decision support. The paper’s context focuses on digital transformations of business and IT and integrates fundamental mappings between adaptable digital enterprise architectures and service-oriented information systems. We are putting a spotlight on the example domain – Internet of Things

Efeitos do repouso e do exercício no solo e na água em hipertensos e normotensos Effects of rest and exercise on ground and in water in hypertensive and normotensive patients

Este estudo visou avaliar o efeito do repouso e do exercício, realizados no solo e na água, sobre a frequência cardíaca (FC), pressão arterial sistólica (PAS) e diastólica (PAD) e o volume de diurese em indivíduos hipertensos e normotensos. Foram analisados 20 indivíduos divididos em dois grupos, normotensos (GN, n=8) e hipertensos (GH, n=12). Em ambos foram realizados quatro protocolos distintos, dois de exercícios e dois de repouso, no solo e na água. A PAS, PAD e FC foram mensuradas durante repouso e aos 30, 60 e 90 minutos após cada protocolo. O volume de diurese foi corrigido pelo peso corporal e coletado 30 minutos após cada protocolo. No GH, o protocolo de exercício no solo promoveu redução média de 16,5±3,7 mmHg (p=0,01) da PAS aos 90 minutos pós-exercício. No GN, o protocolo de repouso na água promoveu redução média de 14 bpm (p<0,01) da FC e o volume de diurese foi maior quando comparado aos protocolos realizados no solo (p<0,01). Portanto, a imersão desencadeou bradicardia e aumento do volume de diurese no GN. Não houve efeito hipotensor significativo nos protocolos realizados na água em ambos os grupos. Os resultados sugerem que uma sessão de exercício físico no solo com duração de 45 minutos, em intensidade submáxima, provoca redução da PAS em indivíduos hipertensos.<br>The aim of this study was to assess the effect of rest and exercise, accomplished on the ground or in water on the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the volume of diuresis in hypertensive and normotensive individuals. Twenty individuals were analyzed and divided into two groups, normotensive (GN, n=8) and hypertensive (GH, n=12). Both groups accomplished four distinct protocols, two protocols of exercise and two protocols of rest on the ground and in the water. The SBP, DBP and HR were measured at rest and at 30, 60 and 90 minutes after each protocol. The volume of diuresis was corrected for the body weight and collected 30 minutes after each protocol. In the GH, the exercise protocol on the ground caused an average reduction of 16.5±3.7 mmHg (p=0.01) in SBP at 90 minutes post-exercise. In the GN, the protocol of rest in the water caused an average reduction of 14 bpm (p<0.01) in HR and the volume of diuresis was increased when compared with the protocols accomplished on the ground (p<0.01). Therefore, the immersion triggered bradycardia and increase in volume of diuresis in the normotensive group. There was no significant hypotensive effect in the protocols performed in water in both groups. The results suggest that an exercise session on the ground during 45 minutes in submaximal intensity causes a reduction in SBP in hypertensive subjects